CD19-Specific T-cells in Treating Patients With Advanced Lymphoid Malignancies

PRIMARY OBJECTIVES:

I. To determine the safety and maximum tolerated dose of genetically modified, CD19-specific T cells administered into patients with CD19+ advanced lymphoid malignancies.

SECONDARY OBJECTIVES:

I. To screen for the development of host immune responses against the CD19-specific chimeric antigen receptor (CAR).

II. To describe the homing ability of the infused T cells. III. To assess disease response. IV. To determine persistence of CAR+ T cells.

OUTLINE: This is a dose escalation study of CD19 positive chimeric antigen receptor T-cells.

LYMPHODEPLETING CHEMOTHERAPY: Patients may receive standard chemotherapy comprised of fludarabine phosphate intravenously (IV) over 1 hour and cyclophosphamide IV over 3 hours on days -5 to -3 or cyclophosphamide IV every 12 hours on days -5 to -3 at the discretion of the treating physician.

Within 30 days post completion of lymphodepletion, patients receive CD19 positive chimeric antigen receptor T-cells IV over 15-30 minutes on day 0, or split into two portions on days 0 and 1.

After completion of study treatment, patients are followed up for at least 15 years.

Inclusion criteria

• Patients with a history of CD19+ lymphoid malignancy defined as acute lymphoblastic leukemia, acute biphenotypic leukemia, non-Hodgkin's lymphoma, small lymphocytic lymphoma, or chronic lymphocytic leukemia with active disease defined by presence of > 5% malignant blasts in bone marrow and/or peripheral blood, and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins, and/or positive imaging for extramedullary disease; patients must have measurable disease at time of study treatment
• Confirmed history of CD19 positivity by flow cytometry for malignant cells
• Lansky/Karnofsky performance scale > 60%
• Patient able to provide written informed consent; parent or guardian of minor patient able to provide written informed consent
• Patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676; parent or guardian of minor patient able to provide written informed consent for the long-term follow-up gene therapy study: 2006-0676

Exclusion criteria

• Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females
• Patients with known allergy to bovine or murine products
• Positive serology for human immunodeficiency virus (HIV)
• Active hepatitis B or active hepatitis C
• Has received donor lymphocyte infusion (DLI) product within 6 weeks of CAR T cell infusion
• Has received allogeneic hematopoietic stem cell transplant within 3 months of CAR T cell infusion; hematopoietic stem cell transplant (HSCT) > 3 months from CAR T cell infusion eligible